Abstract: Objective: To investigate the pathogenesis of brain injury induced by hyperoxia in the newborn rats,to elucidate the mechanism of the protect effect of prostaglandin E1 (PGE-1) through endoplasmic reticulum stress(ERS) pathway,and to provide the relevant theoretical basis for the treatment of brain injury of the newborns induced by hyperoxia. Methods: Ninety newborn Wistar rats were randomly divided into control group,hyperoxia group and hyperoxia+PGE-1 group,and there were 30 rats in each group.The rats in hyperoxia group and hyperoxia+PGE-1 group were placed in the hyperoxia box; the rats in control group were placed under the same room pressure conditions.From the 1st day of modeling,the PGE-1 was intraperitoneally injected into the rats in hyperoxia+PGE-1 group.The rats in the other two groups were injected with the same dose of normal saline.On the 1st,3rd and 7th days of hyperoxia exposure,10 rats in each group were randomly selected to detect the body weights and water contents of brain tissue;the morphology of brain tissue of the rats in three groups was observed by HE staining;the apoptosis of brain cells of the rats in three groups was observed by TUNEL staining,and the apopotic indexes were caculated;the expression amount of c-Jun N-terminal protein kinase(JNK) and phosphorylated JNK(p-JNK) proteins in brain tissue of the rats in three groups were detected by Western blotting method. Results: On the 1st,3rd and 7th days,the body weights of the rats in hyperoxia group were significantly lower than those in control group (P<0.05);the water contents in brain tissue of the rats in hyperoxia group were significantly higher than those in control group (P<0.05);compared with hyperoxia group,the body weights of the rats in hyperoxia+PGE-1 group were increased (P<0.05), and the water contents in brain tissue were decreased (P<0.05). The HE staining results showed that the cerebral cortex cells of the rats in control group were regular in shape and arranged in order,with little infiltration of inflammatory cells and edema of cells;the cortical cells of the rats in hyperoxia group were disordered,and the inflammatory cells were found in the brain parenchyma;the cerebral cortex cells of the rats in hyperoxia+PGE-1 group were arranged neatly,the cell morphology was relatively regular,the number of inflammatory cells in brain parenchyma were reduced,and the degree of brain parenchyma edema was less than that in hyperoxic group.The TUNEL staining results showed that the cells in brain tissue of the rats in control group were mainly cerebral cortical cells,and the apoptotic cells were rare and the nucleus showed homogeneous blue;in hyperoxia group,the nucleus was bright white,which were positive apoptotic cells.Compared with hyperoxia group,the number of apoptotic cells in hyperoxia+PGE-1 group was decreased significantly at the same time point.The apoptotic index in brain cells of the rats in hyperoxia group was higher than those in hyperoxia+PGE-1 group and control group (P<0.05).The expression amounts of JNK and p-JNK proteins in brain tissue of the rats in hyperoxia group were significantly higher than those in control group (P<0.05),and the expression amounts of JNK and p-JNK proteins in brain tissue of the rats in hyperoxia+PGE-1 group were significantly lower than those in hyperoxia group (P<0.05). Conclusion: The pathogenesis of brain injury induced by hyperoxia in the newborn rats may be related to the down-regulation of the expressions of ESR-related p-JNK and JNK proteins,and PGE-1 has the protective effect on it.

Key words: hyperoxic brain injury, endoplasmic reticulum stress, prostaglandin E1, newborn rats